antitumoral efficacy of the protease inhibitor gabexate mesilate in colon cancer cells harbouring kras, braf and pik3ca mutationsantitumoral功效的蛋白酶抑制剂在结肠癌细胞窝藏喀斯特gabexate甲磺酸盐,braf和pik3ca基因突变.pdf

Antitumoral Efficacy of the Protease Inhibitor Gabexate Mesilate in Colon Cancer Cells Harbouring KRAS, BRAF and PIK3CA Mutations 1,2 2,3 1 1 1 Giovanni Brandi *, Simona Tavolari , Francesco De Rosa , Stefania Di Girolamo , Valentina Agostini , 1 1 1,2 Maria Aurelia Barbera , Giorgio Frega , Guido Biasco ` 1 ‘‘L. and A. Seragnoli’’ Department of Hematology and Oncological Sciences, Sant’Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy, 2 ‘‘G. Prodi’’ Interdepartmental Center for Cancer Research (C.I.R.C.), University of Bologna, Bologna, Italy, 3 Center for Applied Biomedical Research (C.R.B.A.), Sant’Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy Abstract The employment of anti-epidermal growth factor receptor (EGFR) antibodies represents a backbone of the therapeutic options for the treatment of metastatic colorectal cancer (mCRC). However, this therapy is poorly effective or ineffective in unselected patients. Mutations in KRAS, BRAF and PIK3CA genes have recently emerged as the best predictive factors of low/absent response to EGFR-targeted therapy. Due to the need for efficacious treatment options for mCRC patients bearing these mutations, in this short report we examined the antitumoral activity of the protease inhibitor gabexate mesilate, alone and in combination with the anti-EGFR monoclonal antibody cetuximab, in a panel of human CRC cell lines harbouring a different expression pattern of wild-type/mutated KRAS, BRAF and PIK3CA genes. Results obtained showed that gabexate mesilate significantly inhibited the growth, invasive potential and tumo